1. Field of the Invention
The invention relates to nanomagnets and methods of using nanomagnets for biological problems, such as the detection and manipulation of biological molecules and nanosurgery within cells.
2. Description of the Prior Art
Magnetic nanostructures have in the past been fabricated for dense storage media and compact magnetic sensors. As the focus of biological analysis turns to progressively smaller sample volumes, and eventually to single molecules, efforts in nanomanipulation, characterization, and local sensing of biological materials become increasingly important. The integration of nanomagnetic devices into biological research instrumentation will provide powerful new capabilities for sensitive, compact and efficient bio-sensing.
Consider first recent advances in magnetic manipulation technology. Within the past 20 years, the micromanipulation and characterization of objects ranging in size from atomic to micrometer dimensions has become one of the central goals of modern science. Scanning tunneling microscopy and atomic force microscopy enable surface imaging with atomic resolution, as well as atomic manipulation in many environments. Optical trapping methods have also become routine for the manipulation of micron-sized latex spheres attached to objects of biological interest. Similarly, carbon nanotubes are utilized for physical tweezing of micro-objects. Magnetic tweezers have more recently also been applied to the study of the physical properties of the cytoplasm, mechanical properties of cell surfaces, and elasticity and transport of single DNA molecules For cell studies, most of these techniques rely on the micromanipulation of magnetic particles positioned within a cell wall or bound on the surface of a cell. For single molecule investigations, magnetic particles are attached onto one end of a molecule strand. In all of these studies, micromanipulation is typically performed with a magnetic manipulator consisting of permanent or soft coil-wound magnets with macroscopic dimensions.
Nanofluidic chips have been developed in which subnanoliter fluid volumes can be manipulated and biochemical assays performed. See, Unger M. A. Science V. 288, pp 113 (2000). These fluidic circuits can be monolithically integrated with optoelectronic sensors to enable the rapid analysis of 10 pL fluid volumes. Thousands of valves and pumps, made in silicone elastomer, have been aligned onto micro-optic chips such as light emitters or silicon CMOS detector arrays to form nanofluidic analysis systems. The integration of optoelectronics with microfluidics has thus allowed the construction of very compact nanofluidic test systems, where the fluidic structures are inexpensive and disposable. The resulting multifunctional biosensor chips are very compact and can concentrate and measure pathogens or toxins as well as deliver drugs. In turn, these nanofluidic systems are ideal for extracting, delivering and holding single cells for high resolution cellular magnetic resonance imaging (cMRI) and for the manipulation of magnetic nanoprobes.
The invention is a new synergy between biology and magnetic nanostructure design by combining (A) capabilities in nanofabrication, characterization, and manipulation of single domain magnetic nanostructures, with (B) the use of binding chemistry of biological molecules to modify the magnetic nanostructures into magnetic sensors and magnetically controllable nanoprobes. The biological characterization scheme of the invention combines nanomanipulation with the observation of small magnetic structures in fluids. These capabilities allow the construction of fundamentally new magnetic nanostructure geometries that are not easily fabricated by conventional high resolution lithographic methods. By coating nanomagnets with biologically interesting molecules and using the approaches detailed below, ultra-small, highly sensitive and robust biomagnetic devices are defined, and molecular electronics and spin electronics are combined. When these nano-sensors are integrated into microfluidic channels, highly efficient single-molecule detection chips for rapid diagnosis and analysis of biological agents are constructed.
As described below a tool is provided to remotely control the position of magnetic nanoparticles, to pattern magnets lithographically onto chips for magnetic self-assembly, and to suspend magnetic wires into cantilevers. By combining these capabilities, a new generation of sensors and imaging instruments is made possible. These structures are especially useful for the nano-manipulation of magnetic probes in-situ within living biological systems, namely performing nanosurgery within cells or within nanofluidic channels, since the magnets can be remotely actuated and controlled by nanocoil probes as described below in connection, which nanocoil probes locally concentrate magnetic fields.
Together with surface plasmon scatterers, which can be attached to the magnetic nanoparticles, the control coils can be used to move magnets within fluids and optically monitor their precise location without the scattering, heating and bleaching often encountered when using optical tweezer technology.
Moreover, magnetic attraction can be used to self-assemble tunnel junctions and define sensitive nanomechanical structures where magnetic forces can be externally applied to add mechanical gain to cantilevers and increase the effective Q of nanomechanical resonators.
Together with our microfluidic tools to hold biological specimens, miniaturized coils are ideally suited for improving the imaging resolution of cMRI systems for cell development studies, since nanocoils can operate at high frequencies and can establish large gradient fields.
In the illustrated embodiment nanomagnetic and nano-optic manipulators and sensors are combined with the previously developed with microfluidic design technology discussed above. What results is the highest resolution magnetic resonant imaging systems yet devised to date, with an ability to manipulate magnetic nanoparticles and trigger biological reactions within a cell. Further, the highest resolution nano-mechanical resonator sensor built to date for detecting electron spin is realized.
One illustrated embodiment of the invention is a magnetic nanoprobe for use in magnetic micromanipulation comprising a micron-sized soft-ferromagnetic wire serving as a magnetic core, a micron-sized coil wound around the magnetic core, and a sharp tip defined on a distal end of the magnetic core.
In one embodiment the micron-sized coil is comprised of at least two layers of wire coils. The micron-sized magnetic core has a diameter of 100 xcexcm or less, the micron-sized coil is comprised of magnet wire having a diameter of 50 xcexcm or less, and the sharp tip defined on a distal end of the magnetic core is formed by electrochemical etching.
The invention can also be described in another embodiment as a method comprising the steps of providing a biofunctionalized magnetically interactive nanoparticle, disposing the biofunctionalized magnetically interactive nanoparticle into a cell, and manipulating the magnetically interactive nanoparticle in the cell by means of a magnetic nanoprobe to interact with intracellular processes.
The invention is also embodied as a nanoelectromagnetic mechanical apparatus comprising a plurality of nanoprobes combined to form a nanoelectromagnet assembly and at least one magnetic nanowire disposed proximate to the nanoelectromagnet assembly and electromagnetically coupled thereto.
The nanoelectromagnetic mechanical apparatus in one embodiment can be embodied as a nanomotor where the nanoelectromagnet assembly is arranged and configured to serve as a stator, and where the nanowire serves as a rotor. In another embodiment the nanoelectromagnet assembly is arranged and configured to serve as a solenoid coil, and where the nanowire serves as an actuator. In still another embodiment the nanoelectromagnet assembly is arranged and configured to serve as a relay coil, and where the nanowire serves as a relay contact.
The invention is further embodied as an apparatus for providing a nanogap point contact comprising a first magnetic nanowire having at least one associated electrical contact, and a second magnetic nanowire disposed askew to the first magnetic nanowire to form a crossing therebetween and having at least one associated electrical contact. The first and second nanowires touch or nearly touch each other at the crossing, so that magnetoresistance between the first and second nanowires can be measured.
At least one of the first and second nanowires is covered with a molecular substance, whose spin transport properties is to be measured, namely a thin film of the molecular substance.
In one embodiment the crossing of the first and second magnetic nanowires is approximately at right angles and their touching or near touching comprises a point contact. The point contact is capable of single molecule interrogation. The first and second magnetic nanowires are each single domain magnets.
The first and second magnetic nanowires each have a longitudinal axis and the single domain magnets are oriented along the longitudinal axis at zero applied magnetic field. The apparatus further comprises a source of an external applied magnetic field and wherein one of the first and second magnetic nanowires has its longitudinal axis substantially perpendicular the external applied magnetic field.
In still yet another embodiment the invention is an apparatus for providing a nanogap comprising a first magnetic nanowire having at least one associated longitudinal length, and a second magnetic nanowire having at least one associated longitudinal length, the second magnetic nanowire disposed substantially parallel to the first magnetic nanowire by at least in part magnetic self-assembly to form the nanogap between at least a portion of their longitudinal lengths. The first and second nanowires touch or nearly touch each other.
An electrical contact is coupled to each of the first and second nanowires, such that the nanogap between them forms and may be used as an electron tunneling junction. The nanogap is approximately 10 nm across or less. In such an embodiment the apparatus may further comprise a coating of a molecular substance of interest on at least one of the first and second magnetic nanowires so that the electron tunneling junction is formed through the molecular substance of interest. The first and second nanowires may further be comprised of sections of longitudinally sequential plating of with magnetic and nonmagnetic material to assist in control of the magnetic self-assembly. For example, the first and second nanowires in one embodiment are comprised at least in part of gold or silver for enhanced molecular Raman signals when aligned, namely a sequential electrodeposition of nickel, silver or gold and nickel portion. Again, a coating of a molecular substance of interest may be disposed on at least one of the first and second nanowires, including at least part of the silver or gold portion.
In another embodiment the invention is an improvement in an apparatus for performing magnetic resonance force microscopy comprising a nanowire cantilever resonator, and a metal colloidal nanoparticle coupled to the nanowire cantilever resonator as an optical nano-reflector to assist in vibration detection by the apparatus. The apparatus includes a light source, and a source of an external magnetic field, so that the nanowire cantilever resonator comprises a cantilevered magnetic nanowire and the metal colloidal nanoparticle comprises a silver nanosphere attached to the nanowire whereby an increased scattering cross section of the metal colloidal nanoparticle due to its plasmon resonance when illuminated by light renders vibration of the cantilevered magnetic nanowire visible when driven by the external magnetic field. In the illustrated embodiment the cantilevered magnetic nanowire is 50 nm in diameter or less. In one implementation the nanowire cantilever resonator comprises a nonmagnetic nanowire as its proximal portion fabricated with a single domain magnetic nanowire as its distal portion for generation of an ultra-high gradient magnetic field for single spin selection or force detection.
The invention is still further defined as an improvement in an apparatus for performing magnetic resonance imaging (MRI) wherein an MRI imaging coil assembly comprises a first fiber, a second fiber disposed parallel to and proximately adjacent to the first fiber, and at least one coil magnet wrapped on each of the first and second fibers so that at least two coils are approximately parallel and adjacent to each other to provide a high gradient magnetic field. Preferably at least two coil magnets are wound on each fiber and serially coupled together as a pair of coil magnets. Each pair is wound and oriented on its corresponding fiber to provide opposing fields to the adjacent pair of magnet coils. The two imagining directions are provided with the MRI imaging coil assembly. The MRI imaging coil assembly generates a magnetic gradient of the order of 100,000 Gauss/cm.
The invention is also defined as an improvement in an apparatus for performing magnetic resonance imaging (MRI) using scanning probe microscopy comprising a cantilevered fiber, a microcoil wound on an end of the fiber, and a magnetic nanoparticle coupled on the fiber and magnetically coupled to the microcoil for generating high gradient imaging magnetic fields. In the illustrated embodiment the magnetic nanoparticle is ferromagnetic.
In another embodiment the fiber is a capillary tube filled with ferromagnetic material. The capillary tube is 25 microns in diameter or less and the microcoil is 50 microns in diameter or less.
The invention is also to be understood as including within its scope methods for using each of the foregoing apparatus or improvements.
While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 USC 112, are not to be construed as necessarily limited in any way by the construction of xe2x80x9cmeansxe2x80x9d or xe2x80x9cstepsxe2x80x9d limitations, but are to be accorded the full scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents, and in the case where the claims are expressly formulated under 35 USC 112 are to be accorded full statutory equivalents under 35 USC 112. The invention can be better visualized by turning now to the following drawings wherein like elements are referenced by like numerals.